PMID: 1201616Dec 1, 1975Paper

Studies on lung tumours. III. Oxidative metabolism of dimethylnitrosamine by rodent and human lung tissue

Chemico-biological Interactions
L den EngelseP Emmelot

Abstract

The oxidative metabolism of the carcinogen dimethylnitrosamine (DMN) was studied in mouse, rat, hamster and human respiratory tissue. [14C]DMN was purified by Dowex-1-bisulfite column chromatography to remove a contaminant (probably [14C]formaldehyde) interfering with the enzyme assay. Since formaldehyde and methyl carbonium ions - yielding methanol with water - are considered to be the primary products of DMN metabolism, tissue slices were assayed for the production of [14C]CO2 from 14C-labelled methanol, formaldehyde, formate, and DMN. Oxidation of formaldehyde to formate was not, but oxidation of formate to CO2 was very much rate-limiting. This rate-limiting step was circumvented by introducing quantitative chemical oxidation of formate to CO2 by mercury(II)chloride following the enzymic reaction. Since oxidation of methanol to CO2 proved to be insignificant, production of CO2 from DMN by lung tissue enzymes and HgCl2 may serve as a parameter for N-demethylating activity and the production of the suspected carcinogenically active methyl carbonium ions. The DMN-N-demethylating activities of lung tissue slices of two mouse strains with widely different susceptibilities to formation of lung adenomas by DMN differed significantl...Continue Reading

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Citations

Oct 1, 1977·Zeitschrift Für Krebsforschung Und Klinische Onkologie. Cancer Research and Clinical Oncology·A Fridman-ManduzioR Goutier
Oct 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·M B Kroeger-KoepkeC J Michejda
Jan 1, 1978·Journal of Toxicology and Environmental Health·M Ruchirawat, R C Shank
Feb 1, 1982·Environmental Health Perspectives
Jan 1, 1982·Drug Metabolism Reviews·H Autrup
May 1, 1977·CRC Critical Reviews in Toxicology·H Witschi, M G Côte

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